Poster Abstract

March 12, 2010

Differences in Virulence Mechanisms During Oropharyngeal and
Disseminated Candidiasis

Dr. Hyunsook Park
Department of Biological Sciences, Cal State L.A.

Abstract : Candida albicans causes variety of infection with significant
morbidity and mortality in a large, diverse population of immunocompromised
patients. This suggests that C. albicans possesses unique characteristics
that enable it to colonize in the host and cause disease when the host has
immune deficiency. Interestingly, C. albicans interacts with oral epithelial
cells during oropharyngeal candidiasis and with vascular endothelial cells
when it disseminates hematogenously. Particularly, the ability of C.
albicans to adhere, invade and injure human endothelial cells and oral
epithelial cells is believed as a critical step to establish the infection.
We set out to identify C. albicans genes that govern interactions with these
host cells in vitro. The transcriptional response of C. albicans to the FaDu
oral epithelial cell line and primary endothelial cells was determined by
microarray analysis. Contact with epithelial cells caused a decrease in
transcript levels of genes related to protein synthesis and adhesion,
whereas contact with endothelial cells did not significantly influence any
specific functional category of genes. Many genes whose transcripts were
increased in response to either host cell had not been previously
characterized. We constructed mutants with homozygous insertions in 22 of
these uncharacterized genes to investigate their function during
host-pathogen interaction. By this approach, we found that YCK2, VPS51, and
UEC1 are required for C. albicans to cause normal damage to epithelial cells
and resist the antimicrobial peptides. YCK2 is also necessary for
maintenance of cell polarity. VPS51 is necessary for normal vacuole
formation, resistance to multiple stressors, and induction of maximal
endothelial cell damage. UEC1 encodes a unique protein that is required for
resistance to cell membrane stress. Therefore, some C. albicans genes whose
transcripts are increased upon contact with epithelial or endothelial cells
are required for the organism to damage these cells and withstand the
stresses that it likely encounters within during growth in the oropharynx
and bloodstream.